A strong dominant ecotropic MuLV restriction gene (Akvr-1), distinct from Fv-1 and other retrovirus regulatory loci in American laboratory mice, is polymorphic in California Lake Casitas (LC) feral mice (Mus musculus). This gene is defined by its ability to block expression of ecotropic but not amphotropic virus in crosses of AFR inbred mice with LC wild mice. The Akvr-1 gene also apparently restricts expression of other ecotropic viruses, including that of wild mice. Therefore, we want to determine the effect of this locus upon the occurrence in LC wild mice of lymphoma and paralysis, diseases caused by the indigenous ecotropic MuLV. We plan to further characterize and confirm the restriction effect of this locus upon endogenous ecotropic virus expression in Fl hybrids between LC mice of Akvr-1RR genotype and high ecotropic virus expressor strains of inbred mice (Akvr-1SS). We will also determine the restriction effect of this gene upon exogenous infection with ecotropic viruses in vivo and in fibroblastic, neural and hematopoietic cells in vitro. By segregation analysis of chromosomal markers and restriction of ecotropic virus expression in genetic crosses between LC and inbred mice we plan to map the Akvr-1 locus and determine its possible identity with the Fv-4 locus defined in Japanese mice (Mus molossinus). As a model for control of cancer and slow neurologic disease in an outbred species, it should be helpful to learn more about the population genetics and function of this "new" retrovirus regulatory gene present in wild mice.